RRC ID 46249
Author Zhu H, Shen H, Sewell AK, Kniazeva M, Han M.
Title A novel sphingolipid-TORC1 pathway critically promotes postembryonic development in Caenorhabditis elegans.
Journal Elife
Abstract Regulation of animal development in response to nutritional cues is an intensely studied problem related to disease and aging. While extensive studies indicated roles of the Target of Rapamycin (TOR) in sensing certain nutrients for controlling growth and metabolism, the roles of fatty acids and lipids in TOR-involved nutrient/food responses are obscure. Caenorhabditis elegans halts postembryonic growth and development shortly after hatching in response to monomethyl branched-chain fatty acid (mmBCFA) deficiency. Here, we report that an mmBCFA-derived sphingolipid, d17iso-glucosylceramide, is a critical metabolite in regulating growth and development. Further analysis indicated that this lipid function is mediated by TORC1 and antagonized by the NPRL-2/3 complex in the intestine. Strikingly, the essential lipid function is bypassed by activating TORC1 or inhibiting NPRL-2/3. Our findings uncover a novel lipid-TORC1 signaling pathway that coordinates nutrient and metabolic status with growth and development, advancing our understanding of the physiological roles of mmBCFAs, ceramides, and TOR. DOI:http://dx.doi.org/10.7554/eLife.00429.001.
Volume 2
Pages e00429
Published 2013-5-21
DOI 10.7554/eLife.00429
PII 00429
PMID 23705068
PMC PMC3660743
MeSH Animals Animals, Genetically Modified Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Energy Metabolism Glucosylceramides / metabolism* Intestinal Mucosa / metabolism* Intestines / growth & development Larva / growth & development Larva / metabolism Mechanistic Target of Rapamycin Complex 1 Multiprotein Complexes / genetics Multiprotein Complexes / metabolism* Mutation Nutritional Status Signal Transduction* TOR Serine-Threonine Kinases / genetics TOR Serine-Threonine Kinases / metabolism*
IF 7.08
Times Cited 42
WOS Category BIOLOGY
Resource
C.elegans tm1027 tm504